The latest medical research on Immunology & Allergy

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about immunology & allergy gathered by our medical AI research bot.

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Engineering antibody-based molecules for HIV treatment and cure.

Current Opinion in Cell Biology

Immunotherapy strategies alternative to current antiretroviral therapies will need to address viral diversity while increasing the immune system's ability to efficiently target the latent virus reservoir. Antibody-based molecules can be designed based on broadly neutralizing and non-neutralizing antibodies that target free virions and infected cells. These multispecific molecules, either by IgG-like or non-IgG-like in structure, aim to target several independent HIV-1 epitopes and/or engage effector cells to eliminate the replicating virus and infected cells. This detailed review is intended to stimulate discussion on future requirements for novel immunotherapeutic molecules.

Bispecific and trispecific antibodies are engineered as a single molecules to target two or more independent epitopes on the HIV-1 envelope (Env). These antibody-based molecules have increased avidity for Env, leading to improved neutralization potency and breadth compared with single parental antibodies. Furthermore, bispecific and trispecific antibodies that engage cellular receptors with one arm of the molecule help concentrate inhibitory molecules to the sites of potential infection and facilitate engagement of immune effector cells and Env-expressing target cells for their elimination.

Recently engineered antibody-based molecules of different sizes and structures show promise in vitro or in vivo and are encouraging candidates for HIV treatment.

Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV.

Current Opinion in Cell Biology

'Broadly neutralizing antibodies' (bNAbs), are rare HIV-specific antibodies which exhibit the atypical ability to potently neutralize diverse viral isolates. While efforts to elicit bNAbs through vaccination have yet to succeed, recent years have seen remarkable preclinical and clinical advancements of passive immunization approaches targeting both HIV prevention and cure. We focus here on the potential to build upon this success by moving beyond neutralization to additionally harness the diverse effector functionalities available to antibodies via fragment crystallizable-effector (Fc) functions.

Recent studies have leveraged the ability to engineer bNAb Fc domains to either enhance or abrogate particular effector functions to demonstrate that activities such as antibody-dependent cell-mediated cytotoxicity contribute substantially to in-vivo antiviral activity. Intriguingly, recent studies in both nonhuman primates and in humans have suggested that passive bNAb infusion can lead to durable immunity by enhancing virus-specific T-cell responses through a 'vaccinal effect'.

The combination of antibody engineering strategies designed to enhance effector functions, with the broad and potent antigen recognition profile of bNAbs, has the potential to give rise to powerful new therapeutics for HIV. We aim to provide a timely review of recent advances to catalyze this development.

High NNRTI resistance levels in HIV-1 infected Zambian mother-infant pairs.

AIDS

To elucidate relationships in antiretroviral (ARV) resistance between HIV-1 infected mother-infant pairs by defining the resistance profiles in the mothers and infants and quantifying drug resistance prevalence in the pairs post-Option B+ implementation.

DNA was extracted from the DBS, the HIV-1 pol region was amplified, and the purified proviral DNA was sequenced using Sanger sequencing. Drug resistance mutations (DRM) were identified in sequenced DNA using the Stanford HIVdb (https://hivdb.stanford.edu/).

DRM were detected in 45% (44/97) of samples, and these samples were found to harbor resistance to at least two ARVs. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was significantly higher than that of other ARV classes. DRM were detected disproportionately in infants (67%; 33/49) compared to mothers (23%; 11/48), but the magnitude of resistance did not differ when resistance was detected. The disparity in drug resistance profiles was reinforced in pairwise comparison of resistance profiles in mother-infant pairs.

While Option B+ is effective in reducing mother to child transmission (MTCT), in cases where this regimen fails, high level NNRTI resistance is frequently detected in infants. This underscores the importance of pre-treatment drug resistance screening in both mothers and infants and emphasizes the necessary change to protease inhibitor (PI)-based and integrase inhibitor (INI)-based regimens for treatment of HIV-1 infected infants and mothers.

Population attributable fractions of mortality in people living with HIV: roles of delayed ART, hepatitis coinfections and social factors.

AIDS

Despite free access to antiretroviral therapy (ART) from 1996 onward, and treatment for all people living with HIV (PLWHIV) from 2013, mortality in Brazil has not homogeneously decreased. We investigated to what extent delayed ART, hepatitis coinfections and sociodemographic factors predict all-cause mortality in Brazilian PLWHIV.

After multiple imputation, an extended Cox model helped estimate the effects of fixed and time-varying covariates on mortality.

The study population (n = 411,028) were mainly male (61%), Caucasian (55%), ≤40 years (61%), heterosexually HIV-infected (71%), living in the Southeast region (48%) and had basic education (79%). HCV and HBV coinfection prevalences were 2.5% and 1.4%, respectively. During a 4-year median follow-up, 61,630 deaths occurred and the mortality rate was 3.45 [95% confidence interval (CI): 3.42-3.47] per 100 person-years. Older age, male gender, non-Caucasian ethnicity, illiteracy/basic education and living outside the Southeast and Central-West regions were independently associated with increased mortality. The main modifiable predictors of mortality were delayed ART (i.e., CD4 < 200 cells/mm at ART initiation) (adjusted population attributable fraction: 14.20% [95% CI: 13.81-14.59]), being ART-untreated (14.06% [13.54-14.59]), and ART-treated with unrecorded CD4 at ART initiation (5.74% [5.26-6.21]). HCV and HBV coinfections accounted for 2.44% [2.26-2.62] and 0.42% [0.31-0.53] of mortality, respectively.

This study demonstrates that besides early ART and coinfection control, actions targeting males, non-Caucasians and illiterate people and those with basic education are important to reduce avoidable deaths among Brazilian PLWHIV.

Monocyte activation and gut barrier dysfunction in South African youth on art and their associations with endothelial dysfunction.

AIDS

There is evidence for endothelial dysfunction in youth living with perinatally acquired HIV (YLPHIV). However little data exist on its mechanisms.

YLPHIV and age-matched HIV-uninfected (HIV-) youth enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) in South Africa between 9-14 years of age were included. YLPHIV were on antiretroviral therapy (ART) > 6 months with viral load <400 copies/mL at baseline and 24 months. Serum biomarkers of systemic inflammation, monocyte activation, intestinal integrity, and oxidized LDL-cholesterol were measured at baseline and after 24 months. Endothelial function was measured at 24 months using reactive hyperemic index (RHI); endothelial dysfunction was defined as RHI < 1.35. Spearman correlation coefficient and quantile regression were used to examine associations between RHI and different biomarkers.

We included 266 YLPHIV and 69 HIV- participants. At baseline, median (Q1, Q3) age was 12 (11, 13) years and 53% were females. YLPHIV had poorer endothelial function compared to HIV- youth (RHI = 1.36 vs 1.52, p < 0.01). At baseline and 24 months, YLPHIV had higher markers of monocyte activation (sCD14), gut barrier dysfunction (intestinal fatty acid binding protein, IFAB-P) and oxidized LDL cholesterol (p≤0.04) compared to HIV- youth. Among YLPHIV, sCD14 remained associated with endothelial dysfunction after adjusting for age, sex, Tanner stage, and ART duration (β:-0.05, p = 0.01).

Despite viral suppression, South African YLPHIV have poor endothelial function and persistent evidence of monocyte activation and gut barrier dysfunction compared to HIV-youth. The long-term clinical significance of gut integrity and monocyte activation needs to be further assessed in YLPHIV.

Internalized HIV stigma predicts subsequent viremia in US HIV patients through depressive symptoms and ART adherence.

AIDS

We sought to examine the prospective association between internalized HIV stigma and unsuppressed viral load and to investigate whether this relationship was sequentially mediated by depressive symptoms and antiretroviral (ART) adherence.

The Center for AIDS Research Network of Integrated Clinical Systems (CNICS) Patient-Reported Outcomes (PROs) survey measures internalized HIV stigma yearly using a 4-item assessment (response scale 1 = strongly disagree to 5 = strongly agree). We obtained PRO, lab, and appointment data from six CNICS sites. We used multivariable logistic regression to examine the association between mean stigma and subsequent viremia. We then used Bayesian sequential mediation to fit a longitudinal sequential path model spanning four time points to test if depressive symptoms at T1 and ART adherence at T2 mediated the effect of stigma at T0 on viral load at T3, adjusting for baseline covariates.

Between February 2016 - November 2018, 6,859 patients underwent stigma assessment and were 81% cis-men, 38% Black, 16% Latinx, 32% heterosexual-identified, and 49% ≥50 years of age. Mean stigma level was 2.00 (SD 1.08). Stigma was significantly associated with subsequent viremia (aOR = 1.16, 95% CI: 1.05-1.28, p 0.004), as were younger age and Black race. The chained indirect effect from stigma to unsuppressed viral load through depressive symptoms and then adherence was significant (standardized β = 0.002; SD = 0.001).

Internalized HIV stigma positively predicts subsequent viremia through depressive symptoms and ART adherence. Addressing the link between stigma and depressive symptoms could help improve viral suppression.

What we talk about when we talk about durable viral suppression.

AIDS

: As policies built on "Undetectable = Untransmittable" become more popular, use of durable viral suppression (DVS) as an outcome in analyses is in...

Comorbidity Indices in People with HIV and Considerations for COVID-19 Outcomes.

AIDS

To determine comorbidity indices in persons-with-HIV (PWH) and lifestyle-similar HIV-negative controls.

The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI) and the Comorbidity Burden Index (CBI) were compared between older PWH and HIV-negative controls using the Mann-Whitney U test; the magnitude of the difference between groups was quantified using the r effect size.

The 699 PWH and 304 HIV-negative controls were predominantly male (87.5% vs. 64.0%), white (86.3% vs. 90.0%) and had median ages of 57 and 58 years, respectively. Among PWH, the median (interquartile range (IQR)) CD4+ T-cell count was 624 (475, 811) cells/μl; 98.7% were on antiretroviral therapy. The median (IQR) ECI was 0 (0, 8) and 0 (-3, 1), CCI was 2 (1, 5) and 1 (0, 1) and CBI 8.6 (2.2, 16.8) and 5.9 (0.6, 10.8), respectively. Whilst all three indices were significantly higher in PWH than in controls (p < 0.001 for each), the magnitude of the differences between the two groups were small to medium, with effect sizes (95% confidence interval) of 0.21 (0.16, 0.27), 0.38 (0.32, 0.42) and 0.18 (0.11, 0.23), respectively.

These three comorbidity indices are higher in PWH compared to HIV-negative controls, although the magnitude of differences between groups were small. Differences in the ECI, reportedly associated with poorer COVID-19 outcomes, were driven by more individuals with HIV being within the higher end of the range.

Telemedicine Pays: Billing and Coding Update.

Current Allergy and Asthma Reports

Telemedicine is a rapidly growing healthcare sector that can improve access to care for underserved populations and offer flexibility and convenience to patients and clinicians alike. However, uncertainty about insurance coverage and reimbursement policies for telemedicine has historically been a major barrier to adoption, especially among physicians in private practice (the majority of practicing allergists).

The COVID-19 public health emergency has highlighted the importance of telehealth as a safe and effective healthcare delivery model, with governments and payers rapidly expanding coverage and payment in an effort to ensure public access to healthcare in the midst of an infectious pandemic. This comprehensive review of updated telemedicine coverage and payment policies will include a tabular guide on how to appropriately bill and optimize reimbursement for telemedicine services. This review of current trends in telemedicine coverage, billing, and reimbursement will outline the historical and current state of telemedicine payment policies in the USA, with special focus on recent policy changes implemented in light of COVID-19. The authors will also explore the potential future landscape of telehealth coverage and reimbursement beyond the resolution of the public health emergency.

HIV and risk of dementia in older veterans.

AIDS

People living with HIV (PLWH) may be at increased risk for dementia as they age. Surprisingly it remains unclear whether PLWH have higher risk of developing dementia in late life compared to those without. We explored whether HIV-infection is associated with incident dementia diagnosis in older U.S. veterans accounting for potential confounders and competing risk of death.

We included 1114 veterans diagnosed with HIV, ages≥55 years (mean = 62 years, SD = 6), followed in the Veterans Health Administration healthcare system from 2004 to 2015, and a propensity-matched comparison group (n = 1114) without HIV. HIV and dementia diagnoses were determined using electronic medical records. Using Fine-Gray proportional hazards models, we examined whether HIV status was associated with greater risk of incident dementia.

During follow-up (mean = 7 years, SD = 4 from date of HIV diagnosis) 5% of veteran PLWH developed dementia compared to 3% without (p = 0.01). Accounting for the competing risk of death and adjusted for demographics, substance use, education and income, PLWH remained 50% more likely to receive a dementia diagnosis (aHR = 1.50, 95% CI 0.96-2.35). Although, cART exposure was associated with increased risk of incident dementia, this was driven by differences in illness severity as captured by CD4 count. There was no evidence of a differential effect by cART class.

In a cohort of older US veterans, HIV infection increased risk of dementia by 50%, exposure to cART did not offset this risk. It is critical to understand the mechanisms by which HIV increases risk for developing dementia in later life.

Cost-effectiveness of integrated HIV prevention and family planning services for Zambian couples.

AIDS

To present the incremental cost from the payer's perspective and effectiveness of couples' family planning counseling (CFPC) with long-acting reversible contraception (LARC) access integrated with couples' voluntary HIV counseling and testing (CVCT) in Zambia. This integrated program is evaluated incremental to existing individual HIV counseling and testing and family planning services.

We report financial costs of actual expenditures during integrated program implementation and outcomes of CVCT+CFPC uptake and LARC uptake. We model primary outcomes of cost-per-: adult HIV infections averted by CVCT, unintended pregnancies averted by LARC, couple-years of protection against unintended pregnancy by LARC, and perinatal HIV infections averted by LARC. Costs and outcomes were discounted at 3%/year.

Integrated program costs were $3,582,186 (2015 USD), 82,231 couples received CVCT+CFPC, and 56,409 women received LARC insertions. The program averted an estimated 7,165 adult HIV infections at $384/adult HIV infection averted over a 5-year time horizon. The program also averted 62,265 unintended pregnancies and was cost-saving for measures of cost-per-unintended pregnancy averted, cost-per-couple-year of protection against unintended pregnancy, and cost-per-perinatal HIV infection averted assuming 3 years of LARC use.

Our intervention was cost-savings for CFPC outcomes and CVCT was effective and affordable in Zambia. Integrated couples-focused HIV and family planning was feasible, affordable, and leveraged HIV and unintended pregnancy prevention.

Proliferation of HIV-infected renal epithelial cells following virus acquisition from infected macrophages.

AIDS

HIV-1 can infect and persist in different organs and tissues, resulting in the generation of multiple viral compartments and reservoirs. Increasing evidence supports the kidney as such a reservoir. Previous work demonstrated that HIV-1 infected CD4+ T-cells transfer virus to renal tubule epithelial (RTE) cells through cell-to-cell contact. In addition to CD4+ T-cells, macrophages represent the other major target of HIV-1. Renal macrophages induce and regulate inflammatory responses and are critical to homeostatic regulation of the kidney environment. Combined with their ability to harbor virus, macrophages may also play an important role in the spread of HIV-1 infection in the kidney.

Multiparametric histochemistry analysis was performed on kidney biopsies from individuals with HIV-1 associated nephropathy (HIVAN). Primary monocyte-derived macrophages were infected with a (GFP)-expressing replication competent HIV-1. HIV-1 transfer from macrophages to RTE cells was carried out in a co-culture system and evaluated by fluorescence-microscopy and flow-cytometry. Live imaging was performed to assess the fate of HIV-1 infected RTE cells over time.

We show that macrophages are abundantly present in the renal inflammatory infiltrate of individuals with HIVAN. We observed contact-dependent HIV-1 transfer from infected macrophages to both primary and immortalized renal cells. Live imaging of HIV-1 infected RTE cells revealed four different fates: proliferation, hypertrophy, latency and cell death.

Our study suggests that macrophages may play a role in the dissemination of HIV-1 in the kidney and that proliferation of infected renal cells may contribute to HIV-1 persistence in this compartment.